The role of undergraduate teaching, learning and a national prescribing safety assessment in preparation for practical prescribing: UK medical students' perspective.

AIMS: To investigate medical students' perspectives on the influence of their undergraduate course and the UK prescribing safety assessment (PSA) on the acquisition of practical prescribing skills. METHODS: An online questionnaire comprising multiple choice and open-ended questions was available to UK medical students in years 3, 4 and 5. Descriptive statistics and thematic analysis were completed. RESULTS: In total, 1023 medical students from 25 UK medical schools responded: 22% (3rd year), 37% (4th year) and 41% (final year). A minority of medical students believed that their medical course prepared them sufficiently for practical prescribing (36.4%, n = 372, 95% confidence interval [CI] = 32-41%), 52.6%, of students thought that practical prescribing should be introduced into the curriculum earlier (n = 538, CI = 48-57%), and 73.7% reported that a more consistent approach to the teaching and learning of practical prescribing might be beneficial (n = 754, CI = 71-77%). An awareness of the national PSA was high (86.5%, n = 885), particularly amongst final year students (98.3%, n = 413, CI = 97-100%); 67.4% of all students (n = 690, CI = 64-71%) and 72.1% (n = 303) of final year students perceived that the PSA will improve or had improved their practical prescribing skills. CONCLUSIONS: The majority of medical students perceive that their undergraduate course does not adequately prepare them for practical prescribing. Many believe that there is some merit in introducing practical prescribing teaching earlier in the curriculum and medical schools adopting a more consistent approach. Among medical students, the PSA is thought to have a positive influence on prescribing skills learning. These data might be useful in developing a programme of study dedicated to practical prescribing.

Safe prescribing training provision for junior doctors: is this optimal?

BACKGROUND: The aim of this study was to determine the training provisions in practical safe prescribing for foundation doctors in NHS hospitals located in the South Thames region. METHODS: A web-based questionnaire was distributed by e-mail to all 1762 foundation doctors in the South Thames Foundation School (STFS) region. In addition, a separate questionnaire was distributed to prescribing training Leads at 15 NHS Hospital Trusts. Quantitative data were analysed using descriptive statistics and thematic analysis was performed on qualitative data. RESULTS: Trainers: 10 Prescribing Leads (67 %) responded. Of the 9 NHS Trusts that offered safe prescribing training in their induction programme, 5 included a practical prescribing session. By the end of the foundation year, 6 NHS Trusts had provided at least one dedicated practical prescribing session for F1s compared with 2 NHS Trusts for F2s. Trainees: A total of 124 foundation trainees (7.2 %) responded (69 F1s and 55 F2s). 87 % of F1s received dedicated training in safe prescribing at their Trust induction (n = 60) in comparison to 49 % of F2s (n = 27). 80 % of F1s (n = 55) had a practical prescribing session during induction versus 27 % of F2s (n = 15). The difference was significant, X (2) (1, N = 124) = 34.23, p <0.0001. Emerging themes from qualitative data included, recognition of medical education as a continuum, importance of working relationships with pharmacists and neglect of F2s. CONCLUSIONS: There appears to be a lack of emphasis on the training of F2 doctors in practical safe prescribing compared with F1 doctors. There should be standardisation of safe prescribing training provisions, particularly in the induction period and for F2 doctors.

Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance.

RATIONALE: The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. OBJECTIVES: We reexamined the current hypothesis using helium-3 ((3)He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years, during which lung volume nearly quadruples. If new alveolarization does not occur, alveolar size should increase to the same extent. METHODS: Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7-21 years. Using (3)HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of (3)He at FRC (n = 109), and average diffusion distance of helium (X(rms)) by q-space analysis (n = 46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. MEASUREMENTS AND MAIN RESULTS: ADC increased by 0.19% for every 1% increment in FRC (95% confidence interval [CI], 0.13-0.25), whereas the expected change in the absence of neoalveolarization is 0.41% (95% CI, 0.31-0.52). Similarly, increase of (X(rms)) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94-fold (95% CI, 1.64-2.30) across the age range studied. CONCLUSIONS: Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover from early life insults and respond to emerging alveolar therapies. Conversely, drugs, diseases, or environmental exposures could adversely affect alveolarization throughout childhood.

Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum.

Familial juvenile hyperuricaemic nephropathy (FJHN), an autosomal dominant disorder, is caused by mutations in the UMOD gene, which encodes Uromodulin, a glycosylphosphatidylinositol-anchored protein that is expressed in the thick ascending limb of the loop of Henle and excreted in the urine. Uromodulin contains three epidermal growth factor (EGF)-like domains, a cysteine-rich region which includes a domain of eight cysteines and a zona pellucida (ZP) domain. Over 90% of UMOD mutations are missense, and 62% alter a cysteine residue, implicating a role for protein misfolding in the disease. We investigated 20 northern European FJHN probands for UMOD mutations. Wild-type and mutant Uromodulins were functionally studied by expression in HeLa cells and by the use of western blot analysis and confocal microscopy. Six different UMOD missense mutations (Cys32Trp, Arg185Gly, Asp196Asn, Cys217Trp, Cys223Arg and Gly488Arg) were identified. Patients with UMOD mutations were phenotypically similar to those without UMOD mutations. The mutant Uromodulins had significantly delayed maturation, retention in the endoplasmic reticulum (ER) and reduced expression at the plasma membrane. However, Gly488Arg, which is the only mutation we identified in the ZP domain, was found to be associated with milder in vitro abnormalities and to be the only mutant Uromodulin detected in conditioned medium from transfected cells, indicating that the severity of the mutant phenotypes may depend on their location within the protein. Thus, FJHN-causing Uromodulin mutants are retained in the ER, with impaired intracellular maturation and trafficking, thereby indicating mechanisms whereby Uromodulin mutants may cause the phenotype of FJHN.

CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease.

Renal tubular reabsorption is important for extracellular fluid homeostasis and much of this occurs via the receptor-mediated endocytic pathway. This pathway is disrupted in Dent's disease, an X-linked renal tubular disorder that is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. Dent's disease is due to mutations of CLC-5, a chloride/proton antiporter, expressed in endosomes and apical membranes of renal tubules. Loss of CLC-5 function alters receptor-mediated endocytosis and trafficking of megalin and cubilin, although the underlying mechanisms remain to be elucidated. Here, we report that CLC-5 interacts with kinesin family member 3B (KIF3B), a heterotrimeric motor protein that facilitates fast anterograde translocation of membranous organelles. Using yeast two-hybrid, glutathione-S-transferase pull-down and coimmunoprecipitation assays, the COOH terminus of CLC-5 and the coiled-coil and globular domains of KIF3B were shown to interact. This was confirmed in vivo by endogenous coimmunoprecipitation of CLC-5 and KIF3B and codistribution with endosomal markers in mouse kidney fractions. Confocal live cell imaging in kidney cells further demonstrated association of CLC-5 and KIF3B, and transport of CLC-5-containing vesicles along KIF3B microtubules. KIF3B overexpression and underexpression, using siRNA, had reciprocal effects on whole cell chloride current amplitudes, CLC-5 cell surface expression, and endocytosis of albumin and transferrin. Clcn5(Y/-) mouse kidneys and isolated proximal tubular polarized cells showed increased KIF3B expression, whose effects on albumin endocytosis were dependent on CLC-5 expression. Thus, the CLC-5 and KIF3B interaction is important for CLC-5 plasma membrane expression and for facilitating endocytosis and microtubular transport in the kidney.

Mutational analysis of CLC-5, cofilin and CLC-4 in patients with Dent's disease.

BACKGROUND/AIMS: Dent's disease is caused by mutations in the chloride/proton antiporter, CLC-5, or oculo-cerebro-renal-syndrome-of-Lowe (OCRL1) genes. METHODS: Eighteen probands with Dent's disease were investigated for mutations in CLC-5 and two of its interacting proteins, CLC-4 and cofilin. Wild-type and mutant CLC-5s were assessed in kidney cells. Urinary calcium excretion following an oral calcium challenge was studied in one family. RESULTS: Seven different CLC-5 mutations consisting of two nonsense mutations (Arg347Stop and Arg718Stop), two missense mutations (Ser244Leu and Arg516Trp), one intron 3 donor splice site mutation, one deletion-insertion (nt930delTCinsA) and an in-frame deletion (523delVal) were identified in 8 patients. In the remaining 10 patients, DNA sequence abnormalities were not detected in the coding regions of CLC-4 or cofilin, and were independently excluded for OCRL1. Patients with CLC-5 mutations were phenotypically similar to those without. The donor splice site CLC-5 mutation resulted in exon 3 skipping. Electrophysiology demonstrated that the 523delVal CLC-5 mutation abolished CLC-5-mediated chloride conductance. Sixty percent of women with the CLC-5 deletion-insertion had nephrolithiasis, although calcium excretion before and after oral calcium challenge was similar to that in unaffected females. CONCLUSIONS: Three novel CLC-5 mutations were identified, and mutations in OCRL1, CLC-4 and cofilin excluded in causing Dent's disease in this patient cohort.

Competency domains in an undergraduate Objective Structured Clinical Examination: their impact on compensatory standard setting.

CONTEXT: Following a 15-week attachment in paediatrics and child health, general practice and dermatology medical students in their second clinical year at this medical school undertake a high-stakes assessment including an objective structured clinical examination (OSCE). There were 2 hypotheses. Firstly, groups of similar stations map to competency domains identifiable by factor analysis. Secondly, poor performance in individual domains is compensated for by achieving the required standard of performance across the whole assessment. METHODS: A total of 647 medical students were assessed by an OSCE during 5 individual examination sittings (diets) over 2 years. Ten scoring stations in the OSCE were analysed and confirmatory factor analysis performed comparing a 1-factor model (where all the stations are discrete entities related to one underlying domain) with a 3-factor model (where the stations load onto 3 domains from a previously reported exploratory factor analysis). RESULTS: The 3-factor model yielded a significantly better fit to the data (chi(2 )=( )15.3, P < 0.01). Assessing the compensation data of 1 diet, 29 of 127 students failed in 1 or more domains described, whereas only 5 failed if compensation was allowed across all domains. DISCUSSION: Confirmatory factor analysis showed a significant fit of the data to previously described competency domains for a high-stakes undergraduate OSCE. Compensation within but not between competency domains would provide a more robust standard, improve validity, and substantially reduce the pass rate.

Healthy children's identification and risk perception of medicines in England.

BACKGROUND: Children's understanding of medicines has an impact on their behavior toward those medicines, and yet there has been a paucity of studies exploring this area. OBJECTIVES: To assess children's ability to identify and to explore their risk perceptions of medicines. METHODS: One hundred eighty-two children aged 4 to 11 years at 2 primary schools in England completed a worksheet containing photos of foods and pharmaceutical products. Children were asked to identify what the picture showed and classify it as "good for them," "bad for them," or "sometimes good/sometimes bad for them." Responses were marked as correct if they identified an item without the need for exact identification. Where an item was correctly identified, risk perception was analyzed. RESULTS: Children correctly identified 5 of the 7 pictures as a form of medicine (mean=5.10, standard deviation=1.51), and identification was positively correlated with age (ρ=0.59, P<.001). A greater percentage of children correctly identified bicolored capsules (86.3% correct, 95% confidence interval [CI]=81.3-91.3) as medicines than either white (71.4% correct, 95% CI=64.9-78) or pink tablets (33.5% correct, 95% CI=26.7-40.4). There was a significant shift with age in the perceptions of the children as they changed from reporting that medicines were good for them to reporting that they were sometimes good and sometimes bad for them. This held for all medicines (χ(2) tests, P<.05) except for the cream and the inhaler. CONCLUSIONS: As children get older, they become better at identifying medicines, and they become more likely to see their potential risks.